rs587693487
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001105206.3(LAMA4):c.4870A>C(p.Asn1624His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,204 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1624S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA4 | NM_001105206.3 | c.4870A>C | p.Asn1624His | missense_variant | 35/39 | ENST00000230538.12 | |
LOC107986633 | XR_001744299.2 | n.439+1423T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA4 | ENST00000230538.12 | c.4870A>C | p.Asn1624His | missense_variant | 35/39 | 1 | NM_001105206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250970Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135636
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000829 AC: 121AN: 1459962Hom.: 0 Cov.: 32 AF XY: 0.0000922 AC XY: 67AN XY: 726384
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74422
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1JJ Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 07, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 406148). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. This variant is present in population databases (rs587693487, gnomAD 0.03%). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 1617 of the LAMA4 protein (p.Asn1617His). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 18, 2023 | The p.N1617H variant (also known as c.4849A>C), located in coding exon 34 of the LAMA4 gene, results from an A to C substitution at nucleotide position 4849. The asparagine at codon 1617 is replaced by histidine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at